The overall aim of this project is to compare age-related cognitive deficits in non-human primates with the structural status of synaptic elements in hippocampal and cortical regions that critically participate in memory and attention. The cognitive and structural alterations that occur with normal cognitive aging are highly selective, preferentially targeting restricted neural systems. All of the investigations focus on evaluating age-related cognitive and morphological alterations within the same subjects, capitalizing on recent advances in the behavioral assessment of cognitive aging. The project is guided by the working hypothesis that regional synaptic structure is related to the efficiency of specific cognitive processes, and that synaptic alterations participate in the cascade of events responsible for age-related learning and memory impairment. Investigation of the hippocampus and related cortical regions, the frontal cortex, and the basal forebrain cholinergic system will allow us to differentiate their selective vulnerability to aging in relation to cognitive status. The use of modern stereological techniques to evaluate synaptic parameters will allow rigourous quantitative comparisons between structural subtypes (presynaptic boutons, dendritic spines, cholinergic fibers) and regions in relation to the quantitative cognitive data. Taken together, these investigations will substantially contribute to our understanding of relationships between synaptic structure and cognitive systems, and their alterations in primate normal cognitive aging.